Selenoprotein T is a novel OST subunit that regulates UPR signaling and hormone secretion

Selenoprotein T (SeIT) is a recently characterized thioredoxin-like protein whose expression is very high during development, but is confined to endocrine tissues in adulthood where its function is unknown. We report here that SeIT is required for adaptation to the stressful conditions of high hormone level production in endocrine cells. Using immunofluorescence and TEM immunogold approaches, we find that SeIT is expressed at the endoplasmic reticulum membrane in all hormone-producing pituitary cell types. SeIT knockdown in corticotrope cells promotes unfolded protein response (UPR) and ER stress and lowers endoplasmic reticulum-associated protein degradation (ERAD) and hormone production. Using a screen in yeast for SeIT-membrane protein interactions, we sort keratinocyte-associated protein 2 (KCP2), a subunit of the protein complex oligosaccharyltransferase (OST). In fact, SeIT interacts not only with KCP2 but also with other subunits of the A-type OST complex which are depleted after SeIT knockdown leading to POMC N-glycosylation defects. This study identifies SeIT as a novel subunit of the A-type OST complex, indispensable for its integrity and for ER homeostasis, and exerting a pivotal adaptive function that allows endocrine cells to properly achieve the maturation and secretion of hormones.